A Multicenter, Open-Label Retreatment Study of the Safety and Effectiveness of PN40082 for Lip Augmentation
Phase: PHASE3
Conditions: Lip Augmentation
Sponsor: Prollenium Medical Technologies Inc.

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PRO 2018-03 
A Multicenter, Open-Label Retreatment Study of the Safety and Effectiveness of PN40082 
for Lip Augmentation 
Original Protocol 
Clinical Phase 3
 
 
Trial Sponsor: 
Prollenium Medical Technologies Inc.
138 Industrial Parkway North 
Aurora Ontario
L4G 4C3
Canada 
Key Sponsor Contact: 
Ario Khoshbin 
President and CEO 
Original Protocol Date: 
26 September 2018
Protocol Version 2.0
Amendment 01 Date: 
13 November 2018
Confidentiality Statement 
This document contains confidential information of Prollenium Medical Technologies Inc. that 
must not be disclosed to anyone other than the recipient study staff and members of the 
independent ethics committee, institutional review board, or authorized regulatory agencies. This 
information cannot be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of Prollenium Medical Technologies Inc.
 
 

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SYNOPSIS  
Title of Study: A Multicenter, Open-Label Retreatment Study of the Safety and Effectiveness 
of PN40082 for Lip Augmentation  
Name of Sponsor: Prollenium Medical Technologies Inc.
Name of Finished Product: PN40082®
Device Composition: Hyaluronic acid gel with lidocaine (0.3% w/w)
Objectives: To evaluate the safety and efficacy of retreatment with PN40082 for lip 
augmentation.
Study Design: This is a multicenter, open-label clinical study of retreatment of subjects 
seeking lip augmentation who received treatment with either PN40082 or Restylane Silk in 
prior Protocol PRO 2018-02. Subjects meeting the inclusion/exclusion criteria will receive a 
single additional treatment with PN40082. 
Visits and telephone contacts will occur at: 
Visit 1 / Day 1 – baseline and treatment. This is the same visit as Visit 5 (Day 168) 
of Protocol PRO 2018-02.
 -Day 3 (±2 days) – Safety follow-up telephone call
 -Day 14 (±2 days) – Safety follow-up telephone call
Visit 2 / Day 28 (±2 days) / Month 1 – Interim Visit 
Visit 3 / Day 56 (±4 days) / Month 2 – End of Study Visit
 -Day 168 (±7 days) / Month 6 – Safety follow-up telephone call 
Efficacy evaluations are: 
Lip Fullness Grading Scale (LFGS) - overall lip fullness considering both lips 
together, fullness of the upper lip, and fullness of the lower lip 
Perioral lines at rest severity scale (POL) - overall perioral lines at rest severity 
considering both lips together, perioral lines at rest severity of the upper lip, and 
perioral lines at rest severity of the lower lip 
Patient Global Aesthetic Improvement (pGAI) 
Investigator Global Aesthetic Improvement (iGAI) 
Safety will be assessed by monitoring adverse events (AEs) at all study visits. Other safety 
evaluations are lip function, lip sensation, lip texture, lip firmness, lip symmetry, and lip 
movement/function. 
Other evaluations are Investigator Ease of Use Assessment, Swelling Assessment, and Subject 
Satisfaction with Lips Assessment. 
Number of Study Centers: Six (6) sites in the United States 
Duration of Participation: Subjects will participate in the study for approximately 6 months 
from the time they sign the informed consent form (ICF) through the final contact 

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Duration of Study: The study will require approximately 20 months from the beginning to the 
end of the study (first subject signing the ICF to last contact with last subject)
Number of Subjects: Eligible subjects from the PRO 2018-02 study will be encouraged to be 
retreated.  It is anticipated that the number of subjects will be less than the 158 subjects 
enrolled in the PRO 2018-02 study.
Inclusion Criteria:
1. In Protocol PRO 2018-02, met all inclusion/exclusion criteria; received study device, 
completed Visit 5 within the specified window; had LFGS score by the Blinded 
Evaluating Investigator at Visit 3/Month 2 within the specified visit window, and had 
no significant protocol violations that would affect the treatment evaluation. 
2. If female and of childbearing potential, a negative urine pregnancy test at Visit 1/Day 1 
and the subject agrees to use adequate contraception during the study period.  
3. Willing to give written informed consent 
Exclusion Criteria:  
1. Women who are pregnant, lactating, or planning a pregnancy 
Study Device
PN40082: a clear, colorless gel in 1.0 mL pre-filled syringes with 25 mg/mL of stabilized 
hyaluronic acid and lidocaine 0.3% w/w 
Statistical Methods 
Safety and efficacy results will be summarized descriptively for all subjects who receive 
retreatment in this study. Data will be summarized overall and also broken down by the 
treatment arm in PRO 2018-02.
Efficacy Analysis: 
Change from baseline in this study and change from baseline in the prior controlled study will 
be summarized for LFGS and POL. Other efficacy variables include pGAI, iGAI, and 
Swelling Assessment at Visit 3/Month 2. 
Safety Analysis:
Adverse events will be coded to system organ class and preferred terms using the Medical 
Dictionary for Regulatory Activities (MedDRA, Version 20 or higher).
Frequency and percentage of subjects reporting treatment-emergent adverse events (TEAEs) 
will be tabulated overall and for each treatment in PRO 2018-02 by preferred terms and further 
by severity and relationship to study device. In summaries of severity and relationship, 
subjects reporting more than one event in a treatment arm that are mapped to the same 
preferred term will be counted only once in that treatment arm under the strongest severity and 
relationship, respectively. In addition, visual-related TEAEs will be summarized separately by 
preferred term. 
 

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SCHEDULE OF ACTIVITIES
Visit Number (Month)
Visit 1a
Phone 
Contacts
Visit 2
(Mo 1) 
Visit 3
(Mo 2) 
Phone Contact
(Mo 6) 
Unsched 
Visit 
Scheduled Day(s) 
Day 1
Day 3 &  
Day 14 
Day 28
Day 56
Day 168
Scheduling Window
± 7 days
± 2 days
± 2 days 
± 4 days
± 7 days 
Informed consent
X 
Medical history/ demographics
Xb 
 
 
 
Vital Signs 
X 
Vision evaluations (Snellen visual 
acuity, confrontational visual fields, 
ocular motility)c
X 
 
X 
X 
 
Xd
Concomitant medication/ 
Treatment 
X 
X 
X 
X 
X 
X 
Inclusion/exclusion criteria 
review 
X 
 
 
 
 
Urine pregnancy test e
X 
Lip Fullness Grading Scale (LFGS) 
(overall, upper lip, and lower lip) 
X 
X 
X 
 
Xd
Perioral lines at rest severity scale 
(POL) (overall, upper lip, and lower 
lip) 
X 
X 
X 
 
Xd
Treatment with PN40082
X
 
 
 
Investigator Ease of Use Assessment
X 
 
 
 
Patient GAI (pGAI)
X 
X 
X 
Xd
Swelling Assessment 
X 
X 
X 
Xd
Investigator GAI (iGAI) 
X 
X 
X 
Xd
Subject Satisfaction with Lips 
X 
X 
X 
Xd
Lip function 
Xf
 
X 
X 
Xd
Lip sensation  
Xf
 
X 
X 
Xd
Lip texture  
Xf
 
X 
X 
Xd
Lip firmness  
Xf
 
X 
X 
Xd
Lip symmetry 
Xf
 
X 
X 
Xd
Lip movement/function 
Xf
X
X
Xd
Adverse event assessment
X 
X 
X 
X 
X 
X
Subject Diary
Dispense 
 
Collect 
 
Note: The timing of each visit is relative to Day 1, which is defined as the day the subject is treated.
a. This is also Visit 5 of Protocol PRO 2018-02 and assessments performed at that visit do not need to be repeated. 
b. To be updated if/as needed for changes since Visit 1 of PRO 2018-02. 
c. To be performed prior to any treatment and repeated 30 minutes following any treatment and all follow-up visits. 
d. If/as needed 
e. For women of childbearing potential, to be completed prior to enrollment.  
f. To be performed prior to injections 

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TABLE OF CONTENTS 
SIGNATURE PAGE ......................................................................................................................2
1
SYNOPSIS ...............................................................................................................................3
2
SCHEDULE OF ACTIVITIES..............................................................................................5
3
TABLE OF CONTENTS ........................................................................................................6
List of Tables................................................................................................................................8
List of Figures...............................................................................................................................8
4
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS......................................9
5
INTRODUCTION .................................................................................................................10
6
STUDY OBJECTIVES .........................................................................................................10
7
INVESTIGATIONAL PLAN ...............................................................................................10
7.1
Overall Study Design ........................................................................................................10
7.2
Beginning and End of Study.............................................................................................11
7.3
Study Population ...............................................................................................................11
7.3.1
Inclusion Criteria.........................................................................................................11
7.3.2
Exclusion Criteria........................................................................................................11
7.3.3
Subject Withdrawal Criteria........................................................................................12
7.3.4
Replacement of Subjects.............................................................................................12
7.4
Treatments.........................................................................................................................12
7.4.1
Dosage and Formulations............................................................................................12
7.4.2
Study Device Administration ......................................................................................12
7.4.3
Method of Packaging, Labeling, Storage, and Dispensing .........................................14
7.4.4
Study Device Accountability ......................................................................................15
7.4.5
Concomitant Medications ...........................................................................................15
7.4.5.1
Precautions ..........................................................................................................15
7.4.5.2
Medications and Treatments Prohibited During the Study .................................15
7.4.5.3
Concomitant Medications and Treatments Allowed During the Study..............16
7.4.6
Assessment of Compliance .........................................................................................16
7.5
Study Schedule..................................................................................................................16
7.6
Study Procedures ..............................................................................................................17
7.6.1
Study Roles .................................................................................................................17
7.6.2
Written Informed Consent...........................................................................................17
7.6.3
Significant Medical History/Demographic Information .............................................17
7.6.4
Vital Signs...................................................................................................................17
7.6.5
Vision Evaluations ......................................................................................................17
7.6.6
Concomitant Medication/Treatment Review ..............................................................17
7.6.7
Urine Pregnancy Test and Acceptable Contraceptive Methods ..................................18
7.6.8
Lip Fullness Grading Scale .........................................................................................18
7.6.9
Perioral Lines at Rest Severity Scale ..........................................................................18

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7.6.10 Review Inclusion/Exclusion Criteria ..........................................................................18
7.6.11 Patient Global Aesthetic Improvement (pGAI) Score ................................................18
7.6.12 Investigator Global Aesthetic Improvement (iGAI) Score .........................................19
7.6.13 Investigator Ease of Use Assessment..........................................................................19
7.6.14 Swelling Assessment...................................................................................................19
7.6.15 Lip Function Evaluation..............................................................................................20
7.6.16 Lip Sensation Evaluation ............................................................................................20
7.6.17 Lip Texture Evaluation ...............................................................................................20
7.6.18 Lip Firmness Evaluation .............................................................................................20
7.6.19 Lip Symmetry Evaluation ...........................................................................................21
7.6.20 Lip Movement/Function Evaluation ...........................................................................21
7.6.21 Subject Satisfaction with Lips (Visual Analog Scale [VAS]) ....................................22
7.6.22 Subject Diary Card......................................................................................................22
7.6.23 Adverse Events and Serious Adverse Events Assessment..........................................22
7.7
Visit-Specific Procedures ..................................................................................................22
7.7.1
Visit 1/Day 1: Treatment.............................................................................................22
7.7.2
Telephone Contacts on Day 3 and Day 14..................................................................23
7.7.3
Visit 2/Day 28 (± 2 days): Month 1 ............................................................................23
7.7.4
Visit 3/Day 56 (± 4 days): Month 2 End of Study Visit/Early Termination ...............24
7.7.5
Telephone Contact on Day 168 (Month 6) ±7 days ....................................................24
7.7.6
Unscheduled Visit .......................................................................................................24
7.8
Efficacy Endpoints............................................................................................................25
7.9
Assessment of Safety ........................................................................................................25
7.9.1
Safety Endpoints .........................................................................................................25
7.9.2
Other Safety Evaluations.............................................................................................25
7.9.3
Definitions of Terms ...................................................................................................25
7.9.3.1
Adverse Event .....................................................................................................25
7.9.3.2
Suspected Adverse Reaction ...............................................................................26
7.9.3.3
Unexpected Adverse Event .................................................................................26
7.9.3.4
Adverse Events of Special Interest .....................................................................26
7.9.3.5
Serious Adverse Event........................................................................................26
7.9.3.6
Planned Hospitalization ......................................................................................27
7.9.4
Pregnancy....................................................................................................................27
7.9.5
Monitoring Adverse Events ........................................................................................27
7.9.6
Assessment of Adverse Events ...................................................................................28
7.9.6.1
Assessment of Severity.......................................................................................28
7.9.6.2
Assessment of Causality .....................................................................................28
7.9.6.3
Reference Safety Information for Assessing Expectedness of Adverse 
Events ..................................................................................................................28
7.9.7
Reporting Safety Observations ...................................................................................28
7.9.8
Diary Assessments ......................................................................................................30
7.9.9
Criteria for Early Termination of the Study ................................................................30
7.9.10 Withdrawal Due to Safety Observations.....................................................................30
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STATISTICAL METHODS ................................................................................................30
8.1
Analysis Populations .........................................................................................................30
8.2
Efficacy Analysis ..............................................................................................................31

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8.3
Safety Analysis .................................................................................................................31
8.4
Sample Size Determination...............................................................................................31
9
ETHICS..................................................................................................................................31
9.1
Informed Consent..............................................................................................................31
9.2
Institutional Review Board (IRB).....................................................................................31
9.3
Subject Confidentiality .....................................................................................................32
9.4
Study Registration.............................................................................................................32
10 DATA HANDLING AND RECORDKEEPING................................................................32
10.1 Site Regulatory Documents Required for Initiation .........................................................32
10.2 Maintenance and Retention of Records ............................................................................33
10.2.1 Case Report Forms (CRFs) .........................................................................................33
10.2.2 Primary Source Documents.........................................................................................34
10.3 Study Monitoring..............................................................................................................34
10.4 Audits and Inspections ......................................................................................................35
10.5 Modifications to the Protocol............................................................................................35
10.6 Completion of the Study ...................................................................................................35
11 CONFIDENTIALITY, USE OF INFORMATION, AND PUBLICATION ....................35
12 LIST OF REFERENCES .....................................................................................................36
13 INVESTIGATOR AGREEMENT ......................................................................................37
14 APPENDIX 1: FILLER FIRST AID PROTOCOL (CHESTNUT C., 2018) ..................38
15 APPENDIX 2: PN40082 INSTRUCTIONS FOR USE......................................................40
List of Tables 
Table 1.
Lip Texture Scoring Criteria..................................................................................20
Table 2.
Lip Firmness Scoring Criteria................................................................................21
Table 3.
Lip Symmetry Scoring Criteria..............................................................................21
List of Figures
Figure 1 
Visual Analog Scale for Subject Satisfaction ........................................................22

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Term 
Definition 
AE 
adverse event 
CFR 
Code of Federal Regulations 
CRF 
case report form, paper or electronic 
DCF 
data correction form 
EOS 
end of study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
iGAI 
Investigator Global Aesthetic Improvement 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
LFGS 
Lip Fullness Grading Scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
OTC 
over-the-counter 
pGAI 
Patient Global Aesthetic Improvement 
PI 
principal investigator 
POL 
Perioral Lines Severity Scale 
SAE 
serious adverse event 
SAR 
suspected adverse reaction 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
VAS 
visual analog scale 

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INTRODUCTION 
PN40082 is a stabilized hyaluronic acid dermal filler with lidocaine. The purpose of this study is 
to evaluate the efficacy and safety of PN40082 in subjects who received one treatment 6 months 
earlier, with or without a subsequent touch-up treatment, for lip augmentation. 
6 
STUDY OBJECTIVES 
To evaluate the safety and efficacy of retreatment with PN40082 for lip augmentation. 
7 
INVESTIGATIONAL PLAN 
7.1 
Overall Study Design 
This is a multicenter, open-label clinical study of retreatment of subjects seeking lip 
augmentation who received treatment with either PN40082 or Restylane Silk in prior Protocol 
PRO 2018-02. Subjects meeting the inclusion/exclusion criteria will receive a single additional 
treatment with PN40082. 
Visits and telephone contacts will occur at: 
Visit 1 / Day 1 – baseline and treatment. This is the same visit as Visit 5 (Day 168) of 
Protocol PRO 2018-02. 
  -Day 3 (±2 days) - Safety follow-up telephone call 
  -Day 14 (±2 days) – Safety follow-up telephone call 
Visit 2 / Day 28 (±2 days) / Month 1 – Interim Visit 
Visit 3 / Day 56 (±4 days) / Month 2 – End of Study (EOS) Visit 
  -Day 168 (±7 days) – Safety follow-up telephone call 
Efficacy evaluations are: 
Lip Fullness Grading Scale (LFGS) - overall lip fullness considering both lips 
together, fullness of the upper lip, and fullness of the lower lip 
Perioral lines at rest severity scale (POL) - overall perioral lines at rest severity 
considering both lips together, perioral lines at rest severity of the upper lip, and 
perioral lines at rest severity of the lower lip 
Patient Global Aesthetic Improvement (pGAI) 
Investigator Global Aesthetic Improvement (iGAI) 
Safety will be assessed by monitoring adverse events (AEs) at all study visits. Adverse events of 
special interest, including any changes in vision and any events attributable to an embolic or 
ischemic cause (e.g., skin infarction), will be monitored. Other safety evaluations are lip 
function, lip sensation, lip texture, lip firmness, lip symmetry, and lip movement/function. 
.
Other evaluations are Investigator Ease of Use Assessment, Swelling Assessment, and Subject 
Satisfaction with Lips Assessment. 

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7.2
Beginning and End of Study 
A subject is considered to be enrolled in the study when he/she has provided written informed 
consent. 
A subject is considered to have completed the study after he/she has completed the Month 6 
safety telephone call. 
A subject is considered to have withdrawn after he/she has withdrawn consent or has been 
withdrawn under the conditions specified in Section 7.3.3. 
A subject is considered to have been lost to follow-up if he/she cannot be contacted by the 
investigator. The investigator will document efforts to attempt to reach the subject at least twice 
by telephone and will send a certified letter before considering the subject lost to follow-up. The 
end of participation for a subject lost to follow-up is documented as the date of the certified 
letter. 
Each subject will be monitored for the occurrence of AEs, including serious adverse events 
(SAEs), starting immediately after treatment initiation. Each subject will be followed for safety 
monitoring until he/she is discharged from the study. 
Follow-up procedures related to pregnancy, AEs, or SAEs may continue beyond the end of the 
study. 
Each subject will participate in the study for approximately 6 months from the time he/she signs 
the ICF through the final contact. After determination of eligibility at Visit 1/Day 1, each subject 
will be treated with study device. 
It is anticipated that the duration of this study will be 20 months from the beginning to the end of 
the study (first subject signing the ICF to last contact with last subject). 
7.3 
Study Population 
7.3.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for the study: 
1. In Protocol PRO 2018-02, the subject was in the per-protocol population, i.e., met all 
inclusion/exclusion criteria; received study device, completed Visit 5 within the specified 
window; had LFGS score by the Blinded Evaluating Investigator at Visit 3/Month 2, and 
had no significant protocol violations that would affect the treatment evaluation. 
2. If female and of childbearing potential, a negative urine pregnancy test at Visit 1/Day 1 
and the subject agrees to use adequate contraception during the study period
3. Willing to give written informed consent 
7.3.2 Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study:  
1.  Women who are pregnant, lactating, or planning a pregnancy 
 

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7.3.3
Subject Withdrawal Criteria 
A subject may withdraw from the study at any time for any reason. 
A subject will be withdrawn from the study if his/her safety or well-being is determined to be at 
risk. Withdrawal will be made at the discretion of the investigator or at the subject’s request. 
A subject must withdraw from the study for any of the following reasons: 
 The subject or legal representative withdraws consent
 There is a significant protocol violation as determined by the Sponsor or medical 
monitor. 
A subject may be withdrawn from the study for any of the following reasons:
 Lost to follow-up 
 Investigator discretion 
Withdrawal is permanent; after a subject has been withdrawn, he/she will not be allowed to 
enroll again. 
If a subject is withdrawn from the study for any reason, the EOS or Early Termination 
procedures (Visit 3/Month 2) should be completed and any outstanding data and study device 
should be collected. Data, including the date and primary reason for withdrawal, must be 
documented on the EOS case report form (CRF) and source document. 
If a subject withdraws from the study at any time due to an AE, the reason for withdrawal, the 
nature of the AE, and its clinical course must be fully documented. The investigator must strive 
to follow the subject until the AE has resolved, become clinically insignificant, is stabilized, or 
the subject is lost to follow-up. For any SAE, follow procedures provided in Section 7.9.7.
7.3.4 Replacement of Subjects 
A subject who withdraws from the study will not be replaced.  
7.4 
Treatments 
The investigator will take responsibility for and will take all steps to maintain appropriate
records and ensure appropriate supply, handling, storage, distribution, and use of study materials 
in accordance with the protocol and any applicable laws and regulations.
7.4.1
Dosage and Formulations 
PN40082 (manufactured by Prollenium Medical Technologies) is a clear, colorless gel in 1.0 mL 
pre-filled syringes with 25 mg/mL of stabilized hyaluronic acid and lidocaine 0.3% w/w. The 
study device will be provided by the Sponsor. 
7.4.2 Study Device Administration  
All subjects in this study will receive one open-label treatment with PN40082. Subjects will 
maintain the unique subject number previously assigned in Protocol PRO 2018-02. 
The subject should be positioned in a seated position and may be reclined to as much as 45°. 

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Any makeup should be removed with a gentle cleanser or a specific makeup remover product 
(such as Neutrogena Cleansing Makeup Remover Facial Wipes).
The non-vermillion areas of the upper and lower lips should be prepared by gentle washing with 
a surgical scrub product (Chlorhexidine, Technicare, etc.). 
To prepare the syringes for use, the investigator should attach one of the needles included in the 
subject study device kit in a firm manner. The plunger should be gently depressed to express any 
unwanted air until a small droplet of implant material appears at the tip of the needle.  
Study device is administered using only a needle provided in the subject study device kit. The 
needle is inserted at an approximate angle of 30° parallel to the surface of the skin or lip. For 
rhytids, study device should be injected into the mid-to-deep dermis. Study device should be 
injected into the submucosal layer for lip augmentation; care should be taken to avoid 
intramuscular injection. If study device is injected too superficially this may result in visible 
lumps and/or bluish discoloration. 
Inject study device applying light to moderate, even pressure on the plunger. Avoid injecting 
quickly as rapid injection can result in increased pain. It is important that the injection is stopped 
just before the needle is pulled out of the skin to prevent material from leaking out or being too 
superficially implanted into the skin. 
Only correct or augment to 100% of the desired volume effect. Do not overcorrect or overfill.  
The needle may be replaced as needed to ensure subject comfort. Only needles provided in the 
subject study device kit may be used. Before needle replacement, the plunger should be 
withdrawn slightly and once the needle has been replaced, the plunger re-advanced to ensure that 
the new needle is prefilled with implant material prior to restarting injections. 
Typical usage for each treatment session is specific to the site as well as the amount of 
augmentation or rhytids correction desired. Based on U.S. clinical studies, the maximum volume 
allowed per treatment is 1.5 mL per lip (1.5 for upper, 1.5 for lower) and 1.0 mL for perioral 
rhytid correction. Thus, the maximum amount that can be used at one treatment session is 4.0 ml. 
Amounts of material injected should be recorded separately for the upper lip, lower lip and 
perioral areas. 
INJECTION TECHNIQUES 
1. Study device can be injected by a number of different techniques that depend on the 
treating investigator’s experience and preference and subject characteristics. 
2. Serial puncture involves multiple, closely spaced injections along wrinkles, folds, or 
the vermillion border. Although serial puncture allows precise placement of the filler, it 
produces multiple puncture wounds that may be undesirable to some subjects.
3. Linear threading (includes retrograde and antegrade) is accomplished by fully 
inserting the needle into the center of the area to be corrected or augmented and injecting 
the filler along the track as a “thread.” Although threading is most commonly practiced 
after the needle has been fully inserted and is being withdrawn, it can also be performed 
while advancing the needle - antegrade technique). To augment the lip, the retrograde 
linear threading technique is the most advisable. 
4. Serial threading is a technique that utilizes elements of both approaches.

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Note! The correct injection technique is crucial for the final result of the treatment. 
5. The following techniques should be avoided as they may result in an increase in short-
term episodes of bruising, swelling, redness, pain, or tenderness at the injection site:
• 
Dissection of the sub-epidermal plane with lateral movement of the needle –
“fanning” 
• 
Rapid flow rate (> 0.3 mL/min) of implant material injection 
• 
High injection volumes  
• 
The use of needles other than ones provided in the subject study device kit
6. The use of cannulas is prohibited. 
7. When the injection is completed, the treated site should be gently massaged so that it 
conforms to the contour of the surrounding tissues. Massaging that substantially deforms 
the lips or causes blanching of compressed tissues is excessive and should be avoided 
except as described below. 
8.  If excessive material is implanted or irregularly implanted, massage the area somewhat 
more firmly than for the usual implantation procedure to obtain optimal results.
9. If blanching of the tissues is observed during or directly after injection and becomes a 
concern, the area may be gently massaged. If blanching persists, contact the Medical 
Monitor.
10. The lips should be augmented to achieve the maximum desirable appearance for both the 
treating investigator and the subject. Subjects should be provided a small hand mirror to 
observe the results and further injections conducted until maximum benefit has been 
obtained. Care should be taken to ensure that the lips are symmetric from right to left 
and that the upper and lower lips have relative proportionality. 
11. The perioral area should be corrected AFTER the upper and lower lips have been 
corrected. Some correction of perioral rhytids may occur with lip augmentation, thus it is 
best to address any remaining perioral correction needs after the lip injections have been 
completed.   
12. If the treated area is swollen directly after the injection, an ice pack can be applied on the 
site for a short period if the investigator deems it appropriate. Ice should be used with 
caution if the area is still numb from anesthetic to avoid thermal injury. 
13. Subjects should be encouraged to avoid a recumbent position for several hours after 
injections to reduce swelling. The use of ice, cold packs or other therapies to reduce 
swelling should only be performed at instruction of the investigator. The subject should 
be instructed to contact the site if substantial swelling occurs. 
7.4.3 Method of Packaging, Labeling, Storage, and Dispensing 
For PN40082, one 1.0 mL syringe is packaged along with two fine-gauge needles (30G) in an 
easy-open tray. Each syringe is equipped with a Luer-Lok as well as a custom finger grip and 
plunger rod. The syringes contain a peelable label to be placed on the subject record for tracking 
purposes. Two trays are packaged in a carton. A label that includes the protocol number and 
Sponsor name will be attached to each carton.  

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All study device will be stored in a climate-controlled, limited access area. 
The investigator agrees to store and administer the study device only at the site(s) listed on 
Form FDA 1572 (or investigator agreement/statement). The investigator, sub-investigator(s), or 
qualified designees also agree that the study device will be administered only to subjects who 
have provided written informed consent and have met all entry criteria. The study device may 
not be used for any purpose other than as stated in the protocol. 
7.4.4 Study Device Accountability 
Study device will be available on site for each subject. Receipt of study device will be 
documented and confirmed via the Investigational Product Receipt Form. All study device must 
be kept in a locked area with access restricted to designated study personnel in a climate-
controlled, limited access area. The administration of study device will be recorded on the Study 
Device Dispensing Log. The site monitor will periodically check the supply of study device held 
by the investigator or pharmacist to ensure accountability. At study conclusion, all unused 
PN40082 study device will be returned to the Sponsor and documented using the Investigational 
Product Return Form. 
Inventory records must be readily available for inspection by the study monitor and/or auditor, 
and open to inspection by regulatory authorities at any time. 
7.4.5 Concomitant Medications 
All medications and other treatments taken by the subject during the study are to be recorded on 
the CRF using their generic name, if known, with the corresponding indication. The medications 
to be recorded include prescription and over-the-counter (OTC) medications and dietary 
supplements. All medications taken on a regular basis, including vitamins, aspirin, and 
acetaminophen, should be recorded prior to use of the study device. 
The use of any concomitant medication must relate to the subject’s documented medical history, 
prophylaxis, or an AE. 
7.4.5.1 
Precautions 
Subjects should be given the following additional instructions: 
 Subject should minimize or avoid excessive natural or artificial sunlight exposure and 
extreme cold weather 
 Subjects should avoid epilation, laser, mechanical or chemical peeling procedures during 
the study 
7.4.5.2 
Medications and Treatments Prohibited During the Study 
Subjects will be advised to avoid the following for the duration of the study: 
 Facial plastic surgery or permanent facial implants (e.g., polymethylmethacrylate, 
silicone, polytetrafluoroethylene, polyacrylamide, lifting threads) anywhere in the face or 
neck 
 Semi-permanent dermal filler treatment (e.g., calcium hydroxylapatite, poly-L-lactic 
acid) in the lower face (below the orbital rim) 

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 Other hyaluronic acid filler materials or collagen-based filler materials below the orbital 
rim 
 Facial tissue augmentation with fat injections, botulinum toxin injections in the lower 
face (below the orbital rim), mesotherapy, or cosmetic procedures in the face or neck 
(e.g., face-lift, laser, photo-modulation, intense pulsed light, radio frequency, 
dermabrasion, moderate or greater depth chemical peel, microneedling, or other ablative 
procedures) 
 Use of any lip plumping products or devices
 Use of any OTC or prescription, oral or topical, anti-wrinkle products for the lips or 
around the mouth (Subjects who have been on a regimen of such products for at least 
90 days must continue their regimen throughout the study.) 
7.4.5.3 
Concomitant Medications and Treatments Allowed During the Study 
Permitted medications/treatments include any concomitant medication/treatment not listed 
below.  
 Facial plastic surgery or permanent facial implants (e.g., polymethylmethacrylate, 
silicone, polytetrafluoroethylene, polyacrylamide, lifting threads) anywhere in the face or 
neck 
 Semi-permanent dermal filler treatment (e.g., calcium hydroxylapatite, poly-L-lactic 
acid) in the lower face (below the orbital rim)  
Facial tissue augmentation with fat injections, botulinum toxin injections in the lower 
face (below the orbital rim), mesotherapy, or cosmetic procedures in the face or neck 
(e.g., face-lift, laser, photo-modulation, intense pulsed light, radio frequency, 
dermabrasion, moderate or greater depth chemical peel, microneedling, or other ablative 
procedures)  
 Use of any lip plumping products or devices  
 Use of any OTC or prescription oral or topical anti-wrinkle products for the lips or 
around the mouth (Subjects who have been on a stable regimen of such products for at 
least 90 days must continue their regimen throughout the study.) 
7.4.6 Assessment of Compliance 
Administration of the study device by the investigator is documented on the CRF. 
7.5 
Study Schedule 
The visit-by-visit schedule of study activities is provided in Section 2. The timing of each visit is 
relative to Day 1, which is defined as the day the subject is treated in the present open-label 
study.
All visits should be performed within the windows specified on the schedule of study activities. 
Every attempt should be made to have each subject attend each visit as scheduled. If a subject is 
unable to attend a visit within the specified window the visit should be scheduled as closely as 
possible to the applicable window. 

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7.6
Study Procedures 
The schedule of study activities summarizes the study procedures to be performed at each visit. 
Individual study procedures are described below. 
All clinical assessments (LFGS, POL, iGAI, lip function, lip sensation, lip texture, lip firmness, 
lip symmetry, and lip movement/function evaluations) must be conducted by qualified 
investigators listed on Form FDA 1572 who have been delegated these tasks by the principal 
investigator (PI). The PI may delegate this task only to physicians, physician assistants, or nurse 
practitioners who have documented training for this protocol and past experience conducting the 
assessment. 
To minimize variability of evaluations, the same investigator/sub-investigator should perform 
these assessments for any given subject and anticipate evaluating the subject at each visit, to the 
extent possible. 
7.6.1 Study Roles 
As this is an open-label study, there is no distinction between treating and evaluating 
investigators. 
7.6.2 Written Informed Consent 
The study personnel will review the ICF for this study with each subject and give the subject an 
opportunity to have all questions answered before proceeding with any study procedures. A copy 
of the signed ICF will be given to every subject and the original will be maintained with the 
subject’s records. 
7.6.3 Significant Medical History/Demographic Information 
Medical history and demographic information will be updated if/as needed at Visit 1/Day 1 to 
record any changes since Visit 1 in Protocol PRO 2018-02. 
7.6.4 Vital Signs 
Vital signs will be recorded. Vital signs will include sitting blood pressure, temperature, heart 
rate, and respiratory rate.  
7.6.5 Vision Evaluations  
Subjects will be assessed with Snellen visual acuity, confrontational visual fields, and ocular 
motility by a trained evaluator. These assessments will be performed at Visit 1/Day 1 prior to 
treatment and repeated 30 minutes following treatment and at Visit 2/Month 1 and Visit 3/Month 
2.
7.6.6
Concomitant Medication/Treatment Review
Concomitant medications (including prescription, OTC, and dietary supplements taken and other 
treatments and cosmetic products used by the subject) will be reviewed with the subject at each 
study visit and telephone contact.

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7.6.7
Urine Pregnancy Test and Acceptable Contraceptive Methods 
Women of childbearing potential, in addition to having a negative urine pregnancy test at Visit 1/ 
Day 1, must be willing to use an acceptable form of birth control during the study. The following 
are considered acceptable methods of birth control for the purpose of this study: oral 
contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double 
barrier methods (e.g., condom and spermicide), contraceptive injection (Depo-Provera®), IUD, 
hormonal IUD (Mirena®), and abstinence with a documented second acceptable method of birth 
control if the subject becomes sexually active. Subjects entering the study who are on hormonal 
contraceptives must have been on the method for at least 90 days prior to the study and continue 
the method for the duration of the study. Subjects who had used hormonal contraception and 
stopped must have stopped no less than 90 days prior to Visit 1/Day 1. 
7.6.8
Lip Fullness Grading Scale  
The LFGS is a validated 5-point photonumeric rating scale that was developed to objectively 
quantify the 3-dimensional fullness of the lip. The scale ratings are 0 for very thin, 1 for thin, 
2 for moderately thick, 3 for thick, and 4 for full (Carruthers et al, 2008). Photographs illustrating 
the ratings will be provided to each site. The assessments of overall lip fullness considering both 
lips together, fullness of the upper lip, and fullness of the lower lip will be performed at each 
study visit. 
7.6.9 Perioral Lines at Rest Severity Scale 
The POL is a 4-point rating scale that corresponds to the most severe perioral line attribute when 
the subject’s mouth is at rest with the following ratings (Cohen et al, 2014):  
0. None – a mouth with no perioral lines 
1. Mild – a mouth with a few shallow perioral lines 
2. Moderate – a mouth with some moderate lines 
3. Severe – a mouth with many deep lines or crevices 
The assessments of overall perioral lines at rest severity considering both lips together, perioral 
lines at rest severity of the upper lip, and perioral lines at rest severity of the lower lip will be 
performed at each study visit. 
7.6.10 Review Inclusion/Exclusion Criteria 
The inclusion and exclusion criteria will be reviewed by the investigator or qualified designee to 
ensure that the subject qualifies for the study. 
7.6.11 Patient Global Aesthetic Improvement (pGAI) Score
The pGAI score is a 5-point scale with the following categories: 
1. 
Worse – the appearance is worse than the original condition. 
2. 
No change – the appearance is the same as the original condition. 
3. 
Improved – obvious improvement in appearance from the initial condition. A 
touch-up might further improve the result. 

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4. 
Much improved – marked improvement in appearance from the initial condition, but 
not completely optimal. A touch-up might slightly improve the result.
5. 
Very much improved – optimal cosmetic result. 
The pGAI score will be recorded at Visit 2/Month 1 and Visit 3/Month 2. Subjects will be asked 
the question “How would you rate improvement in your appearance compared to your initial 
condition using the scale below?” 
7.6.12 Investigator Global Aesthetic Improvement (iGAI) Score
The iGAI score is a 5-point scale with the following categories: 
1. 
Worse – the appearance is worse than the original condition.
2. 
No change – the appearance is the same as the original condition.
3. 
Improved – obvious improvement in appearance from the initial condition. A 
touch-up might further improve the result. 
4. 
Much improved – marked improvement in appearance from the initial condition, but 
not completely optimal. A touch-up might slightly improve the result. 
5. 
Very much improved – optimal cosmetic result. 
The iGAI score will be assessed at Visit 2/Month 1 and Visit 3/Month 2.  
7.6.13 Investigator Ease of Use Assessment 
The Treating Investigator will assess overall ease of use by the device by circling the appropriate 
number on the numerical rating scale from 0 being not easy to 10 being most easy at 
Visit 1/Day 1. 
7.6.14 Swelling Assessment 
Swelling will assessed by the Investigator at Visit 2/Month 1 and Visit 3/Month 2 using the 5-
point scale with the categories that follow. The Investigator should examine both upper and 
lower lip simultaneously and recall the degree of augmentation originally provided for 
comparison. The subject should not be specifically questioned regarding swelling but if the 
subject spontaneously reports it, such information can be used to assist in selection of a grade for 
swelling. 
0. 
None – No swelling noticeable. Lips appear the same as when originally augmented. 
Any lip enlargement is due to the implanted product only.
1. 
Minimal – Slight enlargement of either lip beyond the originally provided 
augmentation. May or may not be noticeable to the subject but is noticeable to the 
investigator. 
2. 
Mild – Some enlargement of either lip beyond the original augmentation that is 
easily noticeable to the subject, but the lips do not appear abnormally large. 
3. 
Moderate – Significant enlargement of either lip beyond the original augmentation. 
Either lip appears abnormally large. 

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4. 
Severe – Any degree of swelling that substantially interferes with lip function such 
as changes in speech or difficulty eating or drinking.
7.6.15 Lip Function Evaluation 
Lip function will be assessed by the Investigator by the subject’s ability to sip liquid through a 
straw prior to treatment at Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2. 
7.6.16 Lip Sensation Evaluation 
Lip sensation will be assessed by the Investigator and tested via: 1) the monofilament test (a 
subject’s ability to feel the sensation of a 0.4G monofilament at 3 points on the upper lip and 
3 points on the lower lip, and 2) the cotton wisp test (a subject’s ability to feel the sensation of a 
cotton wisp at 3 points on the upper lip and 3 points on the lower lip) prior to treatment at 
Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2. 
7.6.17 Lip Texture Evaluation 
Lip texture will be assessed by the Investigator as normal or abnormal prior to treatment at 
Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2 (Table 1).
Table 1. 
Lip Texture Scoring Criteria
Normal
 
Abnormal
Mild 
Moderate 
Severe 
Texture of the lip is 
even without visible 
undulations or excessive 
coarseness beyond that 
expected for stated age 
The lip shows a single 
area of textural 
irregularity (a small 
papule, area of excess 
smoothness, focal 
absence of 
perpendicular lines) can 
be visualized only with 
close inspection 
The lip shows more than 
one area of textural 
irregularity (a small 
papule, area of excess 
smoothness, focal 
absence of 
perpendicular lines) can 
be visualized only with 
close inspection. 
Or 
The lip shows one area 
of textural irregularity 
(less than ¼ of the lip 
area) at a conversational 
distance. 
The lip shows two or 
more areas of textural 
irregularity (a small 
papule, area of excess 
smoothness, focal 
absence of 
perpendicular lines) can 
be visualized at a 
conversational distance. 
Or 
The lip shows one area 
of textural irregularity 
(more than ¼ of the lip 
area) at conversational 
distance 
7.6.18 Lip Firmness Evaluation
Lip firmness will be assessed by the Investigator as normal or abnormal prior to treatment at 
Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2 (Table 2).

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Table 2.
Lip Firmness Scoring Criteria
Normal
 
Abnormal
Mild 
Moderate 
Severe 
Lip is supple when 
compressed laterally 
and surface distorted 
readily with minimal 
pressure.  Pressure with 
a narrow diameter 
instrument (cotton-
tipped applicator, 
toothpick, etc) causes a 
focal depression in the 
surface of the lip.  Upon 
palpation, lip is absent 
of abnormal structures 
such as scars or lumps; 
normal product feel 
without being visible. 
Lip is slightly firm with 
lateral compression or 
required slightly greater 
than normal pressure to 
distort the surface.  
Upon palpation, an 
abnormal structure such 
as a scar or lump is felt, 
but is not visible. 
Lip is firm with lateral 
compression or requires 
distinctly greater than 
normal pressure to 
distort the surface or 
pressure with a narrow 
diameter instrument 
(cotton-tipped 
applicator or toothpick) 
causes a broader 
depression in the 
surface of the lip.  Upon 
palpation, an abnormal 
structure such as a scar 
or lump is felt and is 
visible. 
Lip is very firm with 
lateral compression or 
requires significantly 
greater than normal 
pressure to distort the 
surface.  Upon 
palpitation, an abnormal 
structure such as a scar 
or lump is felt and is 
visually distracting. 
7.6.19 Lip Symmetry Evaluation
Lip symmetry will be assessed by the Investigator as normal or abnormal prior to treatment at 
Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2 (Table 3).
Table 3. 
Lip Symmetry Scoring Criteria 
Normal
 
Abnormal
Mild 
Moderate 
Severe 
One side of the lip 
balanced or mirrored the 
other side 
One side of the lip 
shows a 1 mm or less 
difference in height or a 
1 mm or less difference 
in the length of the 
vermilion at repose. 
One side of the lip 
shows a 1.1 mm to 2 
mm difference in height 
or a 1.1 to 2 mm 
difference in the length 
of the vermilion at 
repose   
One side of the lip 
shows a greater than 2 
mm difference in the 
height or a greater than 
2 mm difference in the 
length of the vermilion 
at repose. 
7.6.20 Lip Movement/Function Evaluation 
Lip movement/function will be evaluated by the Investigator as normal or abnormal prior to 
treatment at Visit 1/Day 1 and at Visit 2/Month 1 and Visit 3/Month 2 as the subject’s ability to 
pucker lips, blowing and pronunciation of words that begin with the letter “W” such as water, 
work, week and wind.   

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7.6.21 Subject Satisfaction with Lips (Visual Analog Scale [VAS]) 
Subjects will be asked to assess their overall satisfaction with their lips at  using a 100 mm VAS 
scale from 0 = Very Unsatisfied to 100 = Very Satisfied at Visit 2/Month 1 and Visit 3/Month 2 
(Figure 1).   
Figure 1 
Visual Analog Scale for Subject Satisfaction 
 
 
 
  Very  
 
 
 
 
 
 
 Very  
 
          Unsatisfied 
 
 
 
 
 
          Satisfied 
7.6.22 Subject Diary Card 
A diary card will be dispensed to each enrolled subject at Visit 1/Day 1. The subject will be 
instructed to complete the diary card to record any AEs experienced during the 2 weeks after 
receiving treatment. The diary card will be collected at Visit 2/Month 1.  
7.6.23 Adverse Events and Serious Adverse Events Assessment 
See Section 7.9 for instructions on the assessment and reporting of AEs and SAEs and 
Section 7.9.7 for instructions on reporting SAEs to the Sponsor or designee. 
7.7 
Visit-Specific Procedures 
The following sections outline the procedures required at each visit. 
7.7.1 Visit 1/Day 1: Treatment 
This is the same as Visit 5 of Protocol PRO 2018-02 and assessments performed for that study 
(e.g., LFGS and POL assessments) do not need to be repeated for this study. 
 Obtain written informed consent  
 Evaluate inclusion/exclusion criteria 
 Update the medical history and demographic information as needed from that at entry 
to Protocol 2018-02  
 Perform vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
 Vision evaluation (Snellen visual acuity, confrontational visual fields, ocular motility) 
 Obtain/record concomitant medications/treatments  
 Perform urine pregnancy test for all women of childbearing potential  
 LFGS assessment  
 POL assessment 
 Lip function evaluation prior to treatment administration 
 Lip sensation evaluation prior to treatment administration 

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 Lip texture evaluation prior to treatment administration
Lip firmness evaluation prior to treatment administration
Lip symmetry evaluation prior to treatment administration
Lip movement/function prior to treatment administration
Treatment administration 
Vision evaluation (Snellen visual acuity, confrontational visual fields, ocular motility)
 Investigator Ease of Use assessment  
 Assess AEs 
 Dispense subject diary card  
 Schedule next visit 
 Complete CRFs  
7.7.2 Telephone Contacts on Day 3 and Day 14  
 Assess AEs 
 Assess concomitant medications/treatments 
 Confirm adherence to prohibited treatments/medications 
7.7.3 Visit 2/Day 28 (± 2 days): Month 1 
 LFGS assessment  
 POL assessment 
 pGAI assessment 
 iGAI assessment 
 Lip function evaluation  
 Lip sensation evaluation  
 Lip texture evaluation  
 Lip firmness evaluation  
 Lip symmetry evaluation  
 Lip movement/function 
 Vision evaluation (Snellen visual acuity, confrontational visual fields, ocular motility) 
 Assess AEs 
 Swelling assessment 
 Assess concomitant medications/treatments  
 Subject satisfaction with lips (VAS) 

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 Complete CRFs  
7.7.4
Visit 3/Day 56 (± 4 days): Month 2 End of Study Visit/Early Termination 
 LFGS assessment  
POL assessment
pGAI assessment
iGAI assessment
Lip function evaluation 
Lip sensation evaluation 
 Lip texture evaluation  
 Lip firmness evaluation  
 Lip symmetry evaluation  
 Lip movement/function 
 Vision evaluation (Snellen visual acuity, confrontational visual fields, ocular motility)
 Assess AEs 
 Swelling assessment 
 Assess concomitant medications/treatments 
 Subject satisfaction with lips (VAS) 
 Complete CRFs  
7.7.5 Telephone Contact on Day 168 (Month 6) ±7 days  
 Assess AEs 
 Assess concomitant medications/treatments
 Confirm adherence to prohibited treatments/medications
7.7.6
Unscheduled Visit 
An unscheduled visit is allowed at any time if in the investigator’s opinion it is warranted. The 
following procedures may be performed at the Unscheduled Visit if required. 
 LFGS assessment  
 POL assessment 
 pGAI assessment 
 iGAI assessment 
 Lip function evaluation 
 Lip sensation evaluation 

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 Lip texture evaluation 
Lip firmness evaluation
Lip symmetry evaluation
Lip movement/function
Vision evaluation (Snellen visual acuity, confrontational visual fields, ocular motility)
Assess AEs
 Swelling assessment 
 Subject satisfaction with lips (VAS) 
 Assess concomitant medications/treatments 
 Complete CRFs  
7.8 
Efficacy Endpoints 
Efficacy will be evaluated by the LFGS, POL, pGAI, iGAI, and Swelling Assessment.
7.9
Assessment of Safety
7.9.1
Safety Endpoints
Safety of the retreatment with PN40082 will be evaluated by the nature, severity, and frequency 
of treatment-emergent adverse events (TEAEs). All AEs that occur during the study will be 
recorded whether or not they are considered to be related to treatment. A description of the AE 
will be recorded with the date of onset, date of resolution, severity of the AE, relationship to the 
study device, action taken, and the outcome.
7.9.2
Other Safety Evaluations 
Adverse events of special interest, including any changes in vision and any events attributable to 
an embolic or ischemic cause (e.g., skin infarction), will be evaluated. Other safety evaluations 
are lip function, lip sensation, lip texture, lip firmness, lip symmetry, and lip movement/function. 
.
7.9.3
Definitions of Terms 
7.9.3.1 
Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug/device
in humans, whether or not considered drug/device-related (21 Code of Federal Regulations 
[CFR] 312.32 (a) and 803). An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of a drug/device, without any judgment about causality.
Expected adverse events are defined as the events that appeared at injection site subsequent to 
the first injection. Expected adverse events may include but are not limited to bruising, swelling, 
erythema, edema, and inflammation at injection site. 

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7.9.3.2 
Suspected Adverse Reaction
A suspected adverse reaction (SAR) is defined as any AE for which there is reasonable 
possibility that the drug/device caused the AE (21 CFR 312.32 (a)).
7.9.3.3 
Unexpected Adverse Event
An AE or SAR is considered unexpected if it is not consistent with the risk information 
described in the labeling for the study device.
7.9.3.4 
Adverse Events of Special Interest 
Certain events will require more detailed and timely reporting. These include: 
- 
any changes in vision 
- 
any events attributable to an embolic or ischemic cause (e.g., skin infarction)
- 
Any incidence of an event due to an embolic or ischemic cause or visual disturbances 
(including, but not limited to, any loss of vision, blurry vision, double vision, pain in or 
around eye, blind spot or shadow in the visual field, trouble moving eyes, etc.) MUST be 
immediately reported to the Medical Monitor by phone, email or fax. The 
investigator/coordinator must complete the AE source/CRF page and email or fax it to 
the Medical monitor as soon as possible after the investigator or coordinator has become 
aware of its occurrence. These reports will include the depth of injection, the injection 
volume, the symptoms that were observed, the time to onset, time to resolution, and any 
interventions that were implemented. The Sponsor will notify the FDA within 
10 working days. 
In the event of blindness or any ophthalmic signs or symptoms, subjects will undergo immediate 
evaluation by a retina specialist. 
Refer to Appendix 1: Filler First Aid Protocol.  
7.9.3.5 
Serious Adverse Event 
An SAE is defined as any AE or SAR that, in the view of the investigator or Sponsor, results in 
any of the following outcomes (21 CFR 312.32 (a)): 
 Death 
 Life-threatening AE (Note: the term “life-threatening” as used here refers to an event that 
in the view of the investigator or Sponsor places the subject at immediate risk of death at 
the time of the event; it does not include an AE or SAE that, had it occurred in a more 
severe form, might have caused death [21 CFR 312.32(a)]) 
 Inpatient hospitalization or prolongation of existing hospitalization. See exclusion to SAE 
reporting below under Planned Hospitalization. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 Congenital anomaly/birth defect 
 Required intervention to prevent permanent impairment/damage

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 Any “other” important medical event. Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered serious when, 
based upon appropriate medical judgment, they may jeopardize the subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or 
drug abuse. 
7.9.3.6 
Planned Hospitalization 
A hospitalization planned by the subject prior to signing the ICF is considered a therapeutic 
intervention and not the result of a new SAE and should be recorded as medical history. If the 
planned hospitalization or procedure occurs as planned, the record in the subject’s medical 
history is considered complete. However, if the event/condition worsens during the study, it must 
be reported as an AE. 
7.9.4 Pregnancy 
Pregnancies occurring after administration of study device require immediate reporting. They 
must be reported within 24 hours after the investigator has become aware of the pregnancy. A 
pregnancy report will be completed and sent by fax to the Sponsor or designee within 24 hours 
of becoming aware of the pregnancy. The investigator will collect follow-up information 
regarding the outcome of the pregnancy and any postnatal sequelae in the infant that must also be 
reported to the Sponsor or designee. Upon awareness of the outcome of the pregnancy, the 
Principal Investigator or designee must forward a follow-up Pregnancy Report with any relevant 
information to the Sponsor or designee.  
If the outcome of the pregnancy meets the criteria for immediate classification of an SAE (e.g., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly), the investigator will 
report the event by faxing a completed SAE report form to the Sponsor or designee within 
24 hours of being notified of the pregnancy report. 
The subject should immediately be withdrawn from the study. 
7.9.5 Monitoring Adverse Events  
Each subject will be monitored for the occurrence of AEs, including SAEs, immediately after 
treatment initiation. Each subject will be followed for safety monitoring until discharged from 
the study. Follow-up procedures related to pregnancy or AEs or SAEs may continue beyond the 
end of the study. 
Subjects will be questioned and/or examined by the investigator or a qualified designee for 
occurrence of AEs throughout the study. The presence or absence of specific AEs should not be 
elicited from subjects. In addition, subjects will be instructed to record AEs on the subject diary 
card during the 2 weeks after treatment. Subjects having AEs will be monitored with relevant 
clinical assessments and laboratory tests, as determined by the investigator. 
AEs, actions taken as a result of AEs, and follow-up results must be recorded on the CRF, as 
well as in the subject’s source documentation. 

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For all AEs that require the subject to be withdrawn from the study and SAEs, relevant clinical 
assessments will be repeated as clinically appropriate until final resolution or stabilization of the 
event(s). 
7.9.6
Assessment of Adverse Events
7.9.6.1 
Assessment of Severity
Severity of AEs will be graded according to the following definitions: 
Mild: AE that was easily tolerated
Moderate: AE sufficiently discomforting to interfere with daily activity
Severe: AE that prevented normal daily activities 
7.9.6.2 
Assessment of Causality 
A medically qualified investigator must assess the relationship of any AE (including SAEs) to 
the use of the study device as unlikely related, possibly related, or probably related based on 
available information, using the following guidelines:
Unlikely related: no temporal association, or the cause of the event has been identified, or 
the study device cannot be implicated based on available information 
Possibly related: temporal association but other etiologies are likely to be the cause; 
however, involvement of the study device cannot be excluded based on available 
information 
Probably related: temporal association, other etiologies are possible, but unlikely based 
on available information 
7.9.6.3 
Reference Safety Information for Assessing Expectedness of Adverse Events
For reference safety information for assessing the expectedness of an AE for the study device in 
this study, see Appendix 2: PN40082 Instructions for Use. 
7.9.7 Reporting Safety Observations 
Any SAE, whether deemed device-related or not, must be reported to the Sponsor or designee by 
telephone, email, or fax as soon as possible after the investigator or coordinator has become 
aware of its occurrence. The investigator/coordinator must complete a Serious Adverse Event 
(SAE) Form and email or fax it to the Sponsor or designee along with the subject’s Adverse 
Events Log and Concomitant Medications Log within 24 hours of notification of the event. The
Sponsor will notify the FDA of device-related SAEs.
Designee and Sponsor contact details:  

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Evyan Cord-Cruz, MD
Medical Monitor
Direct:  516-338-0647 or 631-
474-8531 ext. 5126 
Cell:  516-982-0677
Fax:  631-474-8534 
Email: 
ecruz@symbioresearch.com
Shanna Smith
Director, Clinical Operations 
Direct:  631-4748531 ext. 
2456
Cell:  215-817-0175
Symbio, LLC
21 Perry Street
Port Jefferson, NY 11777 
Tel:  631-474-8531 
Fax:  631-474-8534
Mr. Ario Khoshbin 
President and CEO
Tel:  905-508-1469
Fax:  905-508-6716 
Suzanne Hair, MPH 
Executive Director Clinical 
Affairs
Tel:  704-544-3431 
Cell:  704-618-2496 
Fax:  704-544-3127 
Prollenium Medical 
Technologies, Inc. 
138 Industrial Parkway North
Aurora Ontario
L4G 4C3
CANADA 
Tel:  905-508-1469 
Fax:  905-508-6716
The investigator must be prepared to supply the medical monitor with the following information:
1. Investigator name and site number 
2. Protocol number 
3. Subject ID (screening/randomization) number 
4. Subject initials and date of birth 
5. Subject demographics 
6. Clinical event 
a. description 
b. date of onset 
c. severity 
d. treatment (including hospitalization) 
e. relationship to study device 
f. action taken regarding study device 
g. if the AE was fatal or life-threatening: 
i. cause of death (whether or not the death was related to study device) 
ii. autopsy findings (if available) 
The Sponsor must submit a written summary of the clinical course of any life-threatening SAE 
and related subject information to the FDA within 7 days. Serious and unexpected AEs that are 
not life-threatening must be reported to the FDA within 15 calendar days. Any serious and 
unexpected AE (including all deaths) must also be reported to the Institutional Review Board 
(IRB) by the investigator according to IRB reporting requirements and documentation of this 
report sent to the Sponsor or designee. 

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The investigator must provide a follow-up written report within 5 calendar days of reporting the 
event to the medical monitor. The written report must contain a full description of the event and 
any sequelae. Subjects who have had an SAE must be followed clinically until all parameters 
(including laboratory) have either returned to normal or are stabilized. 
7.9.8 Diary Assessments 
Diaries will be reviewed by the study staff each time they are returned by a subject. Entries will 
be reviewed for completeness and medical accuracy. Any diary events listed by the subject as 
persisting beyond the final recording day of the diary will be evaluated by the Investigator and 
may be recorded as an AE at the discretion of the Investigator. 
7.9.9 Criteria for Early Termination of the Study 
The trial may be terminated because of safety concerns. If termination is deemed appropriate, 
there will be timely communication with the FDA in accordance with the regulations (21 CFR 
812.150 (devices)). The sponsor, Prollenium Medical Technologies, will initiate discussion as 
soon as possible about the appropriate course of action for the trial in question and for the 
investigational product. There will be immediate follow-up by the company to investigate any 
potential safety concern. 
In the event of a vascular embolic event leading to skin necrosis, vision loss, or stroke, 
enrollment and treatment at the investigational site will be suspended and a root cause 
investigation will be conducted to determine the cause of the embolic event and whether the 
outcome was anticipated (the investigator did not properly follow the treatment SOP) or 
unanticipated (the investigator did properly follow the treatment SOP). If the latter situation is 
observed, the entire study will be immediately suspended and no subjects will be enrolled until 
the event can be properly characterized and an appropriate treatment strategy to avoid this 
unanticipated event can be devised.  
7.9.10 Withdrawal Due to Safety Observations 
See Section 7.3.3 for the criteria for withdrawing a subject. If a subject is withdrawn from the 
study, the activities specified for Visit 3/Month 2 on the schedule of study activities (Section 2 
should be completed if possible. 
8 
STATISTICAL METHODS 
Prior to the database lock, a detailed, finalized Statistical Analysis Plan will be completed and 
placed on file. The Statistical Analysis Plan will contain a more comprehensive explanation than 
that provided here of the methodology used in the statistical analyses, as well as the rules and 
data handling conventions used to perform the analyses and the procedure used to account for 
missing data. Data will be summarized overall and also broken down by the treatment arm in 
PRO 2018-02.  
8.1 
Analysis Populations 
Safety and efficacy results will be summarized descriptively for all subjects who receive 
retreatment in this study.   

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8.2
Efficacy Analysis
Change from baseline in this study and change from baseline in the prior controlled study will be 
summarized for LFGS and POL. Other efficacy variables include pGAI, iGAI, and Swelling 
Assessment at Visit 3/Month 2. 
8.3
Safety Analysis 
Adverse events will be coded to system organ class and preferred terms using the Medical 
Dictionary for Regulatory Activities (MedDRA, Version 20 or higher).
Frequency and percentage of subjects reporting TEAEs will be tabulated overall and for each 
treatment in PRO 2018-02 by preferred terms and further by severity and relationship to study 
device. In summaries of severity and relationship, subjects reporting more than one event in a 
treatment arm that are mapped to the same preferred term will be counted only once in that 
treatment arm under the strongest severity and relationship, respectively. In addition, visual 
related TEAEs will be summarized separately by preferred term. 
8.4 
Sample Size Determination 
The maximum sample size was determined by the number of subjects who competed Protocol 
PRO 2018-02. 
9 
ETHICS 
9.1 
Informed Consent 
The principles of informed consent, according to Food and Drug Administration (FDA) 
regulations and International Council for Harmonization (ICH) guidelines on Good Clinical 
Practice (GCP), will be followed. A copy of the proposed ICF must be submitted with the 
protocol to the IRB for approval. 
The informed consent process must be conducted and the ICF must be signed before each subject 
undergoes any Visit 1 procedures that are performed solely for the purpose of determining 
eligibility for the study, in compliance with 21 CFR Part 50. Each subject’s signed ICF must be 
kept on file by the investigator for inspection by regulatory authorities at any time. A copy of the 
signed ICF will be given to the subject. A notation will be made in the subject’s medical record 
indicating the date and time informed consent was obtained. 
9.2 
Institutional Review Board (IRB) 
The study protocol and ICF must be approved in writing by an appropriate IRB as defined by 
FDA regulations and other applicable requirements prior to enrollment of any study subjects. 
Any changes to the protocol or a change of investigator approved by the Sponsor must also be 
approved by the site’s IRB and documentation of that approval provided to the Sponsor or 
designee. Records of the IRB review and approval of all documents pertaining to this study must 
be kept on file by the investigator and are subject to inspection by regulatory authorities during 
or after completion of the study. SAEs must also be reported to the IRB. 

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Periodic status reports must be submitted to the IRB at least annually, as well as notification of 
completion of the study and a final report within 1 month of study completion or termination. A 
copy of all reports submitted to the IRB must be sent to the Sponsor or designee. 
The investigator will ensure that an IRB that complies with the requirements set forth in 21 CFR 
Part 56 will be responsible for the initial and continuing review and approval of the study. 
9.3 
Subject Confidentiality 
All subject data will be identified only by a subject identification number and subject initials. 
However, in compliance with federal guidelines regarding the monitoring of clinical studies and 
in fulfillment of his/her obligations to the Sponsor, the investigator must permit the study 
monitor, Sponsor representative or auditor, and/or FDA representative or other regulatory 
authority to review the portion of the subject’s medical record that is directly related to the study. 
This shall include all study-relevant documentation including medical history to verify 
eligibility, admission/discharge summaries for hospital stays occurring while the subject is 
enrolled in the study, and autopsy reports if a death occurs during the study. 
As part of the required content of informed consent, each subject must be informed that his or 
her medical chart may be reviewed by the Sponsor, the Sponsor’s authorized representatives, 
FDA or other regulatory authority. If access to the medical record requires a separate waiver or 
authorization, it is the investigator’s responsibility to obtain such permission from the subject in 
writing before the subject is entered into the study. 
9.4 
Study Registration 
The study will be registered by the Sponsor on an appropriate free public website such as 
clinicaltrials.gov, which is a service of the United States National Institutes of Health. 
10 
DATA HANDLING AND RECORDKEEPING 
10.1
Site Regulatory Documents Required for Initiation 
The Sponsor or designee will receive the following documents prior to the initiation of the study: 
 Completed, signed Form FDA 1572 
 Current curricula vitae, signed and dated, for the PI and co-investigators named on Form 
FDA 1572 
 Current license(s) of the PI and co-investigators named on Form FDA 1572 
 Documentation of IRB approval of the study protocol, investigator, and ICF 
 Current IRB membership list 
 A copy of the protocol signature page signed by the PI 
 Original Non-disclosure Agreements for the PI and co-investigators named on Form 
FDA 1572 
 Debarment Certification for the PI and co-investigators named on Form FDA 1572 
 Financial Disclosure Statement for all individuals named on Form FDA 1572 

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10.2
Maintenance and Retention of Records
The study will be conducted according to GCP as outlined in ICH guidelines by the FDA. It is 
the responsibility of the investigator to maintain a comprehensive and centralized filing system 
of all relevant documentation. Investigators will be instructed to retain all study records required 
by the Sponsor and the regulations in a secure and safe facility with limited access. Regulations 
require retention for a period of at least 2 years after marketing approval and notification from 
the Sponsor. These regulatory documents should be retained for a longer period if required by 
local regulatory authorities.  
These records include documents pertaining to the receipt and return of study device, IRB, 
informed consent, source documents, and final signed CRFs. No documents shall be transferred 
from the site or destroyed without first notifying the Sponsor.
10.2.1 Case Report Forms (CRFs)
CRFs for individual subjects will be provided by the Sponsor or designee. CRFs must be legible 
and complete. CRFs for this study will be maintained in a study binder and data recorded on 
2-part NCR paper. One copy will be kept by the investigator and the other copy will be collected 
by the study monitor. All forms should be completed using a black ballpoint pen. Errors should 
be lined out, but not obliterated, and the correction inserted, initialed, and dated by designated 
study personnel. Further data corrections will be performed on special “data correction forms” 
(DCFs) that will be provided to the investigator in case of erroneous or unclear data. The 
investigator will make the correction on the DCF and sign the DCF. The original will be sent to 
the study monitor and a copy retained with the CRFs. 
A CRF must be completed and signed by the investigator for each subject enrolled, including 
those withdrawn from the study for any reason. The reason for withdrawal must be noted on a 
subject’s study termination form. 
CRFs must be kept current to reflect the subject’s status at each phase during the course of the 
study. Subjects are not to be identified on CRFs by name; appropriately coded identification and 
the subject’s initials must be used. The investigator must keep a separate log of the subjects’ 
names and addresses. 
Source documents such as the clinic chart are to be maintained separately from the CRF to allow 
data verification. Because of the potential for errors, inaccuracies, and illegibility in transcribing 
data onto CRFs, originals of laboratory and other test results must be kept on file with the 
subject’s CRF. CRFs, source documents, and copies of test results must be available at all times 
for inspection by the study monitor. The following should also be available for review: 
 Subject Screening Log, which should reflect the reason any subject screened for the study 
was found to be ineligible 
 Delegation of Authority Log, which will list all site personnel with their responsibilities 
as delegated by the PI and their signatures. This log will be maintained at the site 
throughout the study 
 Monitoring Log, which will list the date and purpose of all monitoring visits by the 
Sponsor or designee 
 Enrollment Log, which will list subject initials and start and end dates for all enrolled 
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 Product Inventory/Packing Slip, which will list the total amount of study device shipped 
to the site and received and signed for by the investigator 
 Study Device Dispensing Log, which will list the lot number and total amount of study 
device used for each subject 
 ICF, which must be available for each subject and be verified for proper documentation 
All correspondence
10.2.2 Primary Source Documents 
The investigator must maintain primary source documents supporting significant data for each 
subject’s medical notes. These documents, which are considered “source data,” should include 
documentation of: 
 Demographic information 
 Evidence supporting the indication for which the subject is being studied 
 General information supporting the subject’s participation in the study 
 General history and physical findings 
Hospitalization or Emergency Room records (if applicable)
 Each study visit by date, including any relevant findings/notes by the investigator(s), 
occurrence (or lack) of AEs, and changes in medication usage
Any additional visits during the study
Any relevant telephone conversations with the subject regarding the study or possible 
AEs 
An original, signed ICF for study participation
The investigator must also retain all subject-specific printouts/reports of tests and procedures 
performed as a requirement of the study. During monitoring visits the monitor will validate CRF 
entries against these data sources. 
10.3 
Study Monitoring 
The Sponsor or designee will be responsible for monitoring the study according to GCP and 
applicable regulations. The study will be monitored by a Clinical Research Associate (CRA) in 
compliance with GCP, ICH guidelines, and applicable regulations. The investigator will be 
visited by a CRA prior to the study and at regular intervals during the course of the study. These 
visits are to verify adherence to the protocol. The CRA will review the ICFs and verify CRF 
entries by comparing them with the source documents (hospital/clinic/office records) that will be 
made available for this purpose. The CRA will review the maintenance of regulatory 
documentation and product accountability. The monitor will review the progress of the study 
with the investigator and other site personnel on a regular basis. CRFs may be collected during 
these visits. At the end of the study, a closeout monitoring visit will be performed. Monitoring 
visits will be arranged with site personnel in advance at a mutually acceptable time. Sufficient 
time must be allowed by the site personnel for the monitoring of CRFs and relevant source 
documents. The coordinator and/or investigator should be available to answer questions or 
resolve data clarifications. Adequate time and space for these visits should be made available by 
the investigator and study staff. 

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10.4
Audits and Inspections 
During the course of the study and/or after it has been completed, 1 or more sites may be audited 
by authorized representatives of the Sponsor. The purpose of the audit is to determine whether or 
not the study is being conducted and monitored in compliance with recognized GCP/ICH 
guidelines and regulations. 
Additionally, the study may be inspected by regulatory authorities. These inspections may take 
place at any time during or after completion of the study and are based on local regulations.
10.5
Modifications to the Protocol
The procedures defined in the protocol and CRFs will be carefully reviewed to ensure that all 
parties involved with the study fully understand the protocol. To ensure the validity of the data, 
no deviations from the protocol (with minimal exceptions) may be made unless the issue is broad 
enough to warrant revision of the protocol. Such revisions must be submitted to and have 
documented approval from the Sponsor and IRB prior to implementation. The only circumstance 
in which an amendment may be initiated without prior IRB approval is to eliminate an apparent 
immediate hazard to a subject or subjects. In such a case, however, the investigator must notify 
the Sponsor immediately and the IRB within 5 working days after implementation.
10.6 
Completion of the Study 
The investigator is required to forward CRFs and all other relevant data and records to the 
Sponsor or designee. The investigator will complete and report (submission of CRFs) his/her 
study in satisfactory compliance with the protocol as soon as possible after the completion of the 
study. 
The investigator must submit a final report to the IRB and the Sponsor within 1 month of study 
completion or early termination. 
11 
CONFIDENTIALITY, USE OF INFORMATION, AND PUBLICATION 
All information related to this study that is supplied by the Sponsor and not previously published 
is considered confidential information. This information includes but is not limited to data, 
materials (protocol, CRFs), equipment, experience (whether of a scientific, technical, 
engineering, operational, or commercial nature), designs, specifications, know-how, product 
uses, processes, formulae, costs, financial data, marketing plans and direct selling systems, 
customer lists, and technical and commercial information relating to customers or business 
projections used by the Sponsor in its business. Any data, inventions, or discoveries collected or 
developed as a result of this study are considered confidential. This confidential information 
shall remain the sole property of the Sponsor, shall not be disclosed to any unauthorized person 
or used in any unauthorized manner without written consent of the Sponsor, and shall not be 
used except in the performance of the study. 
The information developed during the course of this study is also considered confidential and 
will be used by the Sponsor in the development of the study medication. The information may be 
disclosed as deemed necessary by the Sponsor. To allow the use of the information derived from 
this study, the investigator is obliged to provide the Sponsor with complete test results and all 
data developed in the study. The information obtained during this study may be made available 
to other investigators who are conducting similar studies. 

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The investigator shall not make any publication related to this study without the express written 
permission of the Sponsor. If the investigator wants to publish or present the results of this study, 
he or she agrees to provide the Sponsor with an abstract, manuscript, and/or presentation for 
review 60 days prior to submission for publication or presentation. The Sponsor retains the right 
to delete confidential information and to object to suggested publication/presentation and/or its 
timing (at the Sponsor’s sole discretion). 
12 
LIST OF REFERENCES 
Carruthers A, Carruthers J, Hardas B, et al. A validated lip fullness grading scale. Dermatol 
Surg. 2008;34 Suppl 2: S161-S166. 
Chestnut C. Restoration of visual loss with retrobulbar hyaluronidase injection after hyaluronic 
acid filler. Dermatol Surg. 2018;44:435-446. 
Cohen JL, Thomas J, Paradkar D, et al. An interrater and intrarater reliability study of 
3 photographic scales for the classification of perioral aesthetic figures. Dermatol Surg. 
2014;40:663-670. 
 
 

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13
INVESTIGATOR AGREEMENT 
 
Protocol Number: 
PRO 2018-03 
Protocol Title: 
A Multicenter, Open-Label Retreatment Study of the Safety and 
Effectiveness of PN40082 for Lip Augmentation 
 
I have carefully read and understand the foregoing protocol and agree that it contains all the 
necessary information for conducting this study safely. I will conduct this study in strict 
accordance with this protocol, ICH guidelines for Good Clinical Practice, the Code of Federal 
Regulations, the Health Insurance Portability and Accountability Act (HIPAA), and local 
regulatory guidelines. I will ensure that the requirements for obtaining informed consent are met. 
I will attempt to complete the study within the time designated. I will ensure that the rights, 
safety, and welfare of subjects under my care are protected. I will ensure control of the devices 
under investigation in this study. I will supervise all testing of the devices involving human 
subjects. I will provide copies of the protocol and all other study-related information supplied by 
the sponsor to all personnel responsible to me who participate in the study. I will discuss this 
information with them to assure that they are adequately informed regarding the device and 
conduct of the study. I agree to keep records on all subject information (case report forms, 
shipment and device return forms, and all other information collected during the study) and 
device disposition in accordance with FDA regulations. I will not enroll any subjects into this 
protocol until IRB approval and sponsor approval are obtained. 
 
 
______________________________________ 
Investigator Name (Print) 
 
 
________________________________________             _____________________ 
Investigator Signature                                                          Date  
 

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14
APPENDIX 1: FILLER FIRST AID PROTOCOL (CHESTNUT C., 2018) 
Materials that are needed on-site: 
 Hyaluronidase (Hylenex) 
Aspirin 325mg
Nitroglycerin paste
Provide the following contacts to subjects and these contacts also posted on-site for easy 
reference: 
Ophthalmologist “on call”
 
Closest ER with stroke management capability with directions to ER
Preparation:
- 
The above materials should be gathered and labeled for emergency use only (to ensure 
they are available should an urgent situation arise). 
- 
Staff should be educated regarding the urgent nature of such an event and the location of 
all materials and contact information.
- 
Investigators may wish to familiarize themselves with the retrobulbar injection technique 
via literature or on line training.   
It is critical to recognize any intravascular events during injections and act quickly to maximize 
likelihood of reversal. As soon as an intravascular is recognized, stop any further injections.
If a skin infarction is identified: 
 Apply nitroglycerin paste – apply liberally to the affected area and massage in gently, 
expect headache complaint from subject but do not withhold the treatment. 
 Massage area to help promoted blood flow 
 Dispense Aspirin 325 mg - Have patient chew this or the aspirin may be placed 
sublingually for maximum rapid absorption 
 If blanching persists, consider infiltration with hyaluronidase 
o Infiltrate in the area where material was being injected – this may allow 
hyaluronidase to enter the same vessel that was inadvertently cannulated.
o Infiltrate in the area of blanching or ischemia as well 
o Inject a minimum of 50 units into each area; investigators are free to use larger 
doses as they see fit. 
o Hyaluronidase may be repeated as needed.
 Hot Packs – Towels or gel packs warmed in a microwave can be applied to the area of 
decreased blood flow. 
 Monitor the subject and the area of blanching ischemia.  If blanching persists after 24 

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hours,– consider hyperbaric oxygen treatments. 
If signs/symptoms of visual changes, opthalmoplegia, blindness, ocular pain (usually 
immediately) occur:
 Dispense Aspirin 325 mg - Have patient chew or place the tablet sublingually for 
maximum rapid absorption 
 Massage the globe with repeated inward compression and release – this may free any 
embolic material 
 Infiltration with hyaluronidase into area being corrected or augmented 
 Have staff call ophthalmology:  Insert physician and cell phone number or on-call 
ophthalmology at nearest center with on-call ophthalmology, and arrange transport 
o Bring hyaluronidase with the subject to the ophthalmologist – at least 300 units. 
 If transport time to ophthalmology or ER is more than 60 minutes, consider performing 
retrobulbar hyaluronidase administration, 300-600 units at inferior, lateral orbital rim 
through orbital septum with 1-1.5 inch 27 gauge needle avoiding globe 
After above measures, expedite to emergency room, the retina can tolerate approximately 90 
minutes of ischemia until damage becomes permanent. 
If stroke symptoms are recognized: 
 Dispense Aspirin 325 mg - Have patient chew this or the aspirin may be placed 
sublingually for maximum rapid absorption 
 Infiltration with hyaluronidase into area being corrected or augmented 
 Call for transport to ER immediately 
 Inform local stroke team during transport 
 
 

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15
APPENDIX 2: PN40082 INSTRUCTIONS FOR USE 
 
PN40082 Injectable Hyaluronic Acid Gel with 0.3% Lidocaine 
 
Caution: Federal Law restricts this device to investigational use. This device is limited by 
Federal (or United States) law to investigational use 
DESCRIPTION 
PN40082 is a gel of hyaluronic acid generated by Streptococcus species of bacteria, chemically 
crosslinked with BDDE, stabilized and suspended in phosphate buffered saline at pH=7 with 
0.3% lidocaine. 
INDICATION 
PN40082 is indicated for submucosal implantation for lip augmentation and dermal implantation 
for correction of perioral rhytids in patients over the age of 21. 
CONTRAINDICATIONS 
 PN40082 is contraindicated for patients with severe allergies manifested by a history of 
anaphylaxis or history or presence of multiple severe allergies. 
 PN40082 contains trace amounts of gram positive bacterial proteins and is 
contraindicated for patients with a history of allergies to such material. 
 PN40082 is contraindicated for patients with bleeding disorders. 
 PN40082 is contraindicated for implantation in anatomical spaces other than the dermis 
or submucosal implantation for lip augmentation. 
 PN40082 should not be used in patients with previous hypersensitivity to local 
anesthetics of the amide type, such as lidocaine. 
WARNINGS 
 Defer use of PN40082 at specific sites in which an active inflammatory process (skin 
eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process 
has been controlled. 
 Injection site reactions (e.g., lip swelling, lip pain, and contusion) to PN40082, including 
short-term minor or moderate inflammatory symptoms starting shortly after treatment of 
lips    
 PN40082 must not be implanted into blood vessels. Localized superficial necrosis and 
scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar 
area. It is thought to result from the injury, obstruction, or compromise of blood vessels.
 Delayed onset inflammatory papules have been reported following the use of dermal 
fillers. Inflammatory papules that may occur rarely should be considered and treated as a 
soft tissue infection. 

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 Injections of 4.0 mL or greater (upper and lower lip combined) per treatment session 
increases the occurrence of injection site reactions. If a volume of more than 3 mL is 
needed to achieve optimal correction, a follow-up treatment session is recommended. 
 As with all dermal filler procedures, PN40082 should not be used in vascular rich areas. 
Use of similar products in these areas, such as glabella and nose, has resulted in cases of 
vascular embolization and symptoms consistent with ocular vessel occlusion, such as 
blindness.   
PRECAUTIONS 
 PN40082 is packaged for single use. Do not resterilize. Do not use if package is opened 
or damaged. 
 The safety or effectiveness of PN40082 for the treatment of anatomic regions other than 
lips or perioral rhytids has not been established in controlled clinical studies. 
 As with all transcutaneous procedures, PN40082 implantation carries a risk of infection. 
Standard precautions associated with injectable materials should be followed. 
 The safety of PN40082 for use during pregnancy, in breastfeeding females or in patients 
under 22 years has not been established, and these individuals are excluded from this 
study. 
 Subjects with known susceptibility to keloid formation are excluded from this study. 
Formation of keloids may occur after dermal filler injections. 
 Hyperpigmentation may occur after dermal filler injections. Subjects with known 
hyperpigmentation are excluded from this study. 
 PN40082 should be used with caution in patients on immunosuppressive therapy.
 Bruising or bleeding may occur at PN40082 injection sites. Patients who have undergone 
therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the 3 
weeks preceding treatment with PN40082 have not been studied.  
 After use, syringes and needles should be handled as potential biohazards. Disposal 
should be in accordance with accepted medical practice and applicable local, state and 
federal requirements. 
 The safety of PN40082 with concomitant dermal therapies such as epilation, UV 
irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in 
controlled clinical trials. 
 Patients should minimize exposure of the treated area to excessive sun, UV lamp 
exposure and extreme cold weather at least until any initial swelling and redness has 
resolved. 
 If laser treatment, chemical peeling or any other procedure based on active dermal 
response is considered after treatment with PN40082, there is a possible risk of eliciting 
an inflammatory reaction at the implant site. This also applies if PN40082 is administered 
before the skin has healed completely after such a procedure. 

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 Injection of PN40082 into patients with a history of previous herpetic eruption may be 
associated with reactivation of the herpes. 
HOW SUPPLIED 
PN40082 is supplied in a disposable glass syringe with a Luer-Lok® fitting. PN40082 is packed 
with two 1.0 mL syringes and two sterilized needle(s) 30 G x ½” in a peel tray contained in a 
carton. A patient record label is a part of the syringe label. This label is to be attached to patient 
records to ensure traceability of the product. The contents of the syringe are sterile.
SHELF LIFE AND STORAGE
PN40082 must be used prior to the expiration date printed on the package. Store at a temperature 
of 5 to 25° C (77° F). Do not freeze. Protect from sunlight.  
Do not use if the package is damaged.  
INJECTION TECHNIQUES 
1. Study device can be injected by a number of different techniques that depend on the 
treating investigator’s experience and preference, and patient characteristics. 
2. Serial puncture involves multiple, closely spaced injections along wrinkles, folds or the 
vermillion border. Although serial puncture allows precise placement of the filler, it 
produces multiple puncture wounds that may be undesirable to some patients. 
3. Linear threading (includes retrograde and antegrade) is accomplished by fully 
inserting the needle into the center of the area to be corrected or augmented and injecting 
the filler along the track as a “thread.” Although threading is most commonly practiced 
after the needle has been fully inserted and is being withdrawn, it can also be performed 
while advancing the needle - antegrade technique). To enhance the lip, the retrograde 
linear threading technique is the most advisable. 
4. Serial threading is a technique that utilizes elements of both approaches.   
 
Note! The correct injection technique is crucial for the final result of the treatment. 
5. The following techniques should be avoided as they may result in an increase in short-
term episodes of bruising, swelling, redness, pain, or tenderness at the injection site: 
 Dissection of the sub-epidermal plane with lateral movement of the needle –
“fanning” 
 Rapid flow rate (>0.3 mL/min) of implant material injection 
 High injection volumes  
 The use of needles other than those provided in the treatment kit 
6. The use of cannulas is prohibited 
7. When the injection is completed, the treated site should be gently massaged so that it 
conforms to the contour of the surrounding tissues.  Massaging that substantially deforms 
the lips, or causes blanching of compressed tissues, is excessive, and should be avoided 
except as described below. 

PRO 2018-03 
Confidential 
Version 2.0 
Protocol 
 
13NOV2018 
43
8. If excessive material is implanted or irregularly implanted, massage the area somewhat 
more firmly than for the usual implantation procedure to obtain optimal results. 
9. If blanching of the tissues is observed during or directly after injection, pause the 
procedure and massage the area gently until the color returns.  If the condition persists, 
contact the Medical Monitor. 
10. The lips should be augmented to achieve the maximum desirable appearance for both the 
treating investigator and the subject.  Subjects should be provided a small hand mirror to 
observe the results and further injections conducted until maximum benefit has been 
obtained.  Care should be taken to ensure that the lips are symmetric from right to left and 
that the upper and lower lips have relative proportionality.  
11. The perioral area should be corrected AFTER the upper and lower lips have been 
corrected.  Some correction of perioral rhytids may occur with lip augmentation, thus it is 
best to address any remaining perioral correction needs after the lip injections have been 
completed.   
12. If the treated area is swollen directly after the injection, an ice pack can be applied on the 
site for a short period. Ice should be used with caution if the area is still numb from 
anesthetic to avoid thermal injury. 
13. Subjects should be encouraged to avoid a recumbent position for several hours after 
injections to reduce swelling.  The use of ice, cold packs or other therapies to reduce 
swelling should only be performed at instruction of the investigator.  The subject should 
be instructed to contact the site if substantial swelling occurs.